The identity, rate of synthesis, and metabolic modification of non-histone chromosomal proteins will be studied in neonatal and regenerating liver and liver neoplasms of the rat in order to characterize those aspects associated with malignant growth. The incorporation of isotope-labeled precursors will be measured in nuclear proteins separated by polyacrylamide gel electrophoresis and isoelectric focusing. To further delineate the relationship between growth rate and non-histone chromosomal proteins, the influence of drugs which inhibit DNA synthesis will be examined. Such studies could reveal the degree of coupling between DNA replication and synthesis of nuclear proteins. Isolation of those nuclear proteins which appear most characteristic of normal liver or liver neoplasms will be performed by preparative gel electrophoresis. If these proteins serve as regulators of gene expression, it may be possible to incubate them with tissue slices and obtain either an increase or decrease of DNA synthesis according to the source of the protein. Alternatively, the injection of nuclear proteins whose levels are diminished in tumors may serve to inhibit tumor growth. The Morris series of transplantable hepatomas will be used in these studies because they provide the opportunity to correlate changes in nuclear proteins with growth rate.